1. Field of the Invention
This invention relates to a method for producing L-3,4 dihydroxyphenylalanine (hereinafter referred to as L-DOPA). L-DOPA is widely used as medicine for treating Parkinson disease.
2. Discussion of the Background
Conventionally, as a method for producing L-DOPA, a synthetic method which uses vanillin as the starting material has been widely known. On the other hand, various methods for producing L-DOPA by utilizing enzymatic systems of a microorganism have been studied, including a method for producing L-DOPA from catechol, pyruvic acid and ammonium ion by utilizing .beta.-tyrosinase (Japanese Patent Publication No. 73-34237; U.S. Patent No. 3,791,924), a method from catechol and L-serine and other amino acids by utilizing .beta.-tyrosinase (Japanese Patent Publication No. 72-22275; U.S. Pat. No. 3,791,924), a method from dihydroxycinnamic acid and ammonium ions by utilizing ammonia-lyase (Japanese Patent Publication No. 87-24076), a method from L-phenylalanine or L-tyrosine by utilizing oxygenase (Japanese Patent Publication Nos. 72-19033 and 72-14915) and a method from 3,4-dihydroxyphenylpyruvic acid by utilizing transaminase (Japanese Patent Publication No. 83-18475).
However, the production of L-DOPA using any of these methods is costly, and there is a need for a method for producing L-DOPA which is both inexpensive and provides high efficiency.
It is an object of the present invention to provide a method for producing L-DOPA which provides lower production cost and higher efficiency as compared with conventionally known methods for producing L-DOPA, by improving a method for producing L-DOPA which utilizes the .beta.-tyrosinase of a microorganism.
As the result of the present research, to improve a method for producing L-DOPA, which utilizes the .beta.-tyrosinase of a microorganism, we have found that the productivity of L-DOPA is largely improved by modifying the preparation method of the culture containing .beta.-tyrosinase, the source of ammonium ion and/or the way of adding the substrates in the reaction mixture. Based on the obtained results, we have completed the present invention.